Comparison of Erythrocyte Differentiation Efficiency and Gene Expression Signatures of Human Induced Pluripotent Stem Cells Derived from Peripheral Blood, Umbilical Cord Blood, and Bone Marrow
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE211625 | GEO | 2022/09/25
REPOSITORIES: GEO
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2016-01-06 | E-GEOD-76526 | biostudies-arrayexpress
Project description:To determine the miRNA expression pattern in RBCs, we isolated miRNA from RBCs of healthy blood donors, who were homozygous or heterozygous carriers of different AB0 blood groups. We first analyzed miRNA expression by microarray chip analysis. In average, we found 873 miRNAs to be present in RBCs with a partially differential expression pattern depending on the blood group genotype. 148 out of these 873 miRNAs were significantly up- or downregulated in RBCs of blood group 0 and of heterozygous genotypes, as compared to homozygous genotypes.
2016-01-06 | GSE76526 | GEO
Project description:Sickle cell disease (SCD) is canonically characterized by reduced red blood cell (RBC) deformability leading to microvascular obstruction and inflammation. While the biophysical properties of sickle RBCs are known to influence SCD vasculopathy, the contribution of poor RBC deformability to endothelial dysfunction has yet to be fully explored. Leveraging interrelated in vitro and in silico approaches, we introduce a new paradigm of SCD vasculopathy in which poorly deformable sickle RBCs directly cause endothelial dysfunction via mechanotransduction, where endothelial cells sense and pathophysiologically respond to aberrant physical forces independently of microvascular obstruction, adhesion, or hemolysis. We demonstrate that perfusion of sickle RBCs or pharmacologically-dehydrated healthy RBCs into small venule-sized “endothelialized” microfluidics leads to pathologic physical interactions with endothelial cells that directly induce inflammatory pathways. Using a combination of computational simulations and large venule-sized endothelialized microfluidics, we observed that perfusion of heterogeneous sickle RBC subpopulations of varying deformability, as well as suspensions of dehydrated normal RBCs admixed with normal RBCs leads to aberrant margination of the less-deformable RBC subpopulations towards the vessel walls, causing localized, increased shear stress. Increased wall stress is dependent on the degree of subpopulation heterogeneity and oxygen tension and leads to inflammatory endothelial gene expression via mechanotransductive pathways. Our multifaceted approach demonstrates that the presence of sickle RBCs with reduced deformability leads directly to pathological physical (i.e., direct collisions and/or compressive forces) and shear-mediated interactions with endothelial cells and induces an inflammatory response, thereby elucidating the ubiquity of vascular dysfunction in SCD.
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Project description:Background: The number of red blood cells (RBCs) increases significantly in response to high-altitude hypoxic environments, and the RBC microRNA (miRNA) expression pattern is similar to that in whole blood. Studies have shown that miRNA in plasma can act as a circulating hypoxia-associated marker, but the effect of a high-altitude hypoxic environment on RBC-derived miRNAs has not yet been reported. Methods: Blood samples were collected from 20 Han Chinese individuals residing at 500 m (Sichuan Han), 10 migrant Han Chinese citizens residing at 3658 m (Tibet Han) and 12 native Tibetans, and RBC indices measurements and miRNA sequencing analyses were performed for the three sample groups. The levels of some markedly altered miRNAs at high altitude were subsequently measured from 5 randomly selected samples of each group by real-time PCR. Bioinformatic analyses was performed to determine the potential target genes of selected hypoxia-associated miRNAs. Results: Marked changes of several RBC indices were observed among the Tibet Han population, the Tibetan population and the Sichuan Han population. A total of 516 miRNAs derived from RBCs were initially identified by miRNA sequencing in the three sample groups. Compared with the Sichuan Han population, 49 miRNAs were differentially expressed in the Tibet Han population (17 upregulated and 32 downregulated). 12 upregulated and 21 downregulated miRNAs were observed in the Tibetan population compared with the Sichuan Han population. A total of 40 RBC miRNAs were differentially expressed in the Tibetan population (15 upregulated and 25 downregulated) compared with the Tibet Han population. Two significantly altered miRNAs with the highest expression levels (miRNA-144-5p and miR-30b-5p) were selected for real-time PCR analysis, and the results were consistent with those of miRNA sequencing. Furthermore, bioinformatic analyses showed that some potential target genes of miR-144-5p and miR-30b-5p are involved in the erythroid- hypoxia-, and nitric oxide (NO)-related signaling pathways in response to hypoxia. Conclusion: Our findings provide clear evidence, for the first time, that a high-altitude hypoxic environment significantly affects human RBC miRNA profiles.
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2022-07-14 | GSE205806 | GEO
Project description:Umbilical cord blood could serve as useful source of blood markers enabling more efficient and reliable prenatal and neonatal diagnostics. MicroRNAs (miRNAs) are ubiquitous in body fluids where they were used for detecting and monitoring various physiological and pathological conditions. In this descriptive study, we aimed to identify changes in miRNA expression profiles associated with basic maternal somatic and epidemiological characteristics.
2019-03-28 | GSE128943 | GEO
Project description:Early diagnosis of hepatocellular carcinoma (HCC) has not been clinically resolved, which has been causing more death in patients with HCC. HCC is a systemic disease related to disorders of blood homeostasis, and the association of red blood cells (RBCs) and HCC tumorigenesis has been still elusive. We performed data independent acquisition (DIA) proteomic analyses with 72 clinical RBCs samples including HCC (n = 30), liver cirrhosis (LC, n = 17) and healthy controls (n = 25), and characterized the clinical relevanve of RBCs and tumorigenesis in HCC. We observed that RBCs dynamically changes during the tumorigenesis of HCC, and LC is a developmental stage closely approaching HCC based on the protein expresson profiles in RBCs. The expression of hemoglobin (HbA, HbF) in peripheral blood dynamically changes during the whole process of HCC tumorigenesis, suggesting immature erythroid cells exist in peripheral blood of HCC patients and erythropoiesis in the patients begins to be influenced with the occurance of LC. We also identified the disturbed autophagy pathway in RBCs with the onset of LC and maintained during the tumorigenesis of HCC. Oxytocin pathway and GnRH pathway are disturbed and first identified during the development of LC into HCC. SMIM1, ANXA7, HBA1 and HBE1 that are significantly altered during tumorigenesis were verified with parallel reaction monitoring (PRM) technology as promising biomarkers for HCC early diagnosis. This study could facilitate the understanding of the tumorigenesis of HCC from a different view and early diagnosis for HCC.
2022-07-21 | PXD035464 |
Project description:Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the “effective dose” of HSCs. Molecular profiling with Affymetrix GeneChips were used to determine the optimal ex vivo modulation conditions (e.g., temperature and media) for use in a clinical setting by measured pathway induced expression changes. Isolated human CD34+ from umbilical cord blood were incubated ex vivo in Stem Span (SS) media evaluating three treatment temperatures (4 deg C, 25 deg C, and 37 deg C) with 10uM 16,16-dmPGE2 or Vehicle (DMSO) for 2 hours. To evaluate optimal media, similar CD34+ cells were incubated ex vivo in either Stem Span-SFEM (SS) media or 8% Low Molecular Weigh Dextran 40/5% HSA solution (LMD/HSA) with 10uM 16,16-dmPGE2 or Vehicle (DMSO) for 2 hours at 37 deg C. Total RNA was isolated post incubation and analyzed on Affymetrix microarrays for pathway activation.
2013-09-12 | E-GEOD-46569 | biostudies-arrayexpress
Project description:Comparison of Erythrocyte Differentiation Efficiency and Gene Expression Signatures of Human Induced Pluripotent Stem Cells Derived from Peripheral Blood, Umbilical Cord Blood, and Bone Marrow
| PRJNA871224 | ENA